ABSTRACT
Testicular cancer seminoma is one of the most common types of cancer among men of reproductive age. Patients with this condition usually present reduced semen quality, even before initiating cancer therapy. However, the underlying mechanisms by which testicular cancer seminoma affects male fertility are largely unknown. The aim of this study was to investigate alterations in the sperm proteome of men with seminoma undergoing sperm banking before starting cancer therapy, in comparison to healthy proven fertile men (control group). A routine semen analysis was conducted before cryopreservation of the samples (n = 15 per group). Men with seminoma showed a decrease in sperm motility (P = 0.019), total motile count (P = 0.001), concentration (P = 0.003), and total sperm count (P = 0.001). Quantitative proteomic analysis identified 393 differentially expressed proteins between the study groups. Ten proteins involved in spermatogenesis, sperm function, binding of sperm to the oocyte, and fertilization were selected for validation by western blot. We confirmed the underexpression of heat shock-related 70 kDa protein 2 (P = 0.041), ubiquinol-cytochrome C reductase core protein 2 (P = 0.026), and testis-specific sodium/potassium-transporting ATPase subunit alpha-4 (P = 0.016), as well as the overexpression of angiotensin I converting enzyme (P = 0.005) in the seminoma group. The altered expression levels of these proteins are associated with spermatogenesis dysfunction, reduced sperm kinematics and motility, failure in capacitation and fertilization. The findings of this study may explain the decrease in the fertilizing ability of men with seminoma before starting cancer therapy.
Subject(s)
Adult , Humans , Male , Acrosin/metabolism , Case-Control Studies , Chaperonin Containing TCP-1/metabolism , Electron Transport Complex III/metabolism , HSP70 Heat-Shock Proteins/metabolism , Peptidyl-Dipeptidase A/metabolism , Proteasome Endopeptidase Complex/metabolism , Proteomics , Semen Analysis , Seminoma/metabolism , Sodium-Potassium-Exchanging ATPase/metabolism , Sperm Count , Sperm Motility , Spermatozoa/metabolism , Testicular Neoplasms/metabolismABSTRACT
ABSTRACT Purpose To determine enzymatic antioxidant and lipid peroxidation levels in seminal plasma of patients orchiectomized for testicular tumors. Materials and Methods The study included 52 patients: 26 control men and 26 orchiectomized patients for testicular tumor, of which 12 men had seminoma tumor and 14 men non-seminoma tumor. After semen analysis performed according to the WHO guidelines, an aliquot of semen was centrifuged and the seminal plasma was collected. Lipid peroxidation was performed by thiobarbituric acid reactive substances (TBARS) assay and antioxidant profile was assessed by analyzing catalase, glutathione peroxidase (GPx) and superoxide anion (SOD) activities using colorimetric assays with a standard spectrophotometer. Data were tested for normality and compared using one-way ANOVA (p<0.05). Results Seminoma and non-seminoma groups presented lower sperm concentration and morphology when compared to control group (p=0.0001). Both study groups (seminoma and non-seminoma) presented higher TBARS levels when compared to control group (p=0.0000013). No differences were observed for SOD (p=0.646) andGPx (p=0.328). It was not possible to access the enzymatic activity of catalase in any group. Conclusion Patients with testicular tumor present increased semen oxidative stress, but no differences were observed in antioxidant levels, even after orchiectomy. This indicates that most likely an increased generation of oxidative products takes place in these patients.
Subject(s)
Humans , Male , Adolescent , Adult , Young Adult , Semen/enzymology , Testicular Neoplasms/metabolism , Lipid Peroxidation/physiology , Seminoma/metabolism , Antioxidants/metabolism , Oligospermia , Sperm Count , Superoxide Dismutase/metabolism , Testicular Neoplasms/surgery , Orchiectomy , Catalase/metabolism , Case-Control Studies , Cross-Sectional Studies , Oxidative Stress/physiology , Semen Analysis , Glutathione Peroxidase/metabolism , Middle AgedABSTRACT
BACKGROUND: Testis-expressed sequence 101 (TEX101) was found to be highly expressed in testis and involved in acrosome reaction in previous studies. Recently, the metastasis suppressor function of TEX101 in cancer was disclosed, but the comprehensive investigation of its expression has rarely been reported. In this study, the expression features of TEX101 in normal human organs and seminoma were systematically analyzed. RESULTS: Immunohistochemistry demonstrated intense staining of TEX101 in human testis tissues; however, its expression in 27 other types of normal human organs, including the ovary, was negligible. Higher expression of TEX101 was observed in the spermatocytes and spermatids of the testis, but relatively lower staining was detected in spermatogonia. Western blotting showed a single TEX101 band of 38 kDa in human testis, but it did not correspond to the predicted molecular weight of its mature form at 21 KDa. Furthermore, we examined seminoma tissues by immunohistochemistry and found that none of the 36 samples expressed TEX101. CONCLUSIONS: Our data confirmed TEX101 to be a testis protein that could be related to the maturation process of male germ cells. The lack of TEX101 in seminoma indicated its potential role in tumor progression. This characteristic expression of TEX101 could provide a valuable reference for understanding its biological functions.
Subject(s)
Humans , Male , Female , Seminiferous Epithelium/metabolism , Testicular Neoplasms/metabolism , Seminoma/metabolism , Membrane Proteins/metabolism , Organ Specificity/physiology , Ovary/metabolism , Seminiferous Epithelium/pathology , Sperm Maturation/physiology , Spermatozoa/growth & development , Testicular Neoplasms/pathology , Testis/metabolism , Testis/pathology , Immunohistochemistry , Cell Differentiation , Blotting, Western , Seminoma/pathology , Gastrointestinal Tract/metabolism , Epithelium/metabolism , Lymphoid Tissue/metabolism , Nerve Tissue/metabolismABSTRACT
Primary testicular tumors are the most common causes of cancer in male dogs. Overall, the majority of canine patients should be cured by testicular surgery. However, tumor markers are not well-known in veterinary medicine. We sought to determine using immunohistochemistry whether the combined human testicular tumor markers (placental alkaline phosphatase, OCT3/4, CD30, alpha-fetoprotein, inhibin-alpha, vimentin, c-KIT, and desmin) are expressed in canine seminomas and Sertoli cell tumors (SCTs). We examined 35 canine testicular tumors, 20 seminomas and 15 SCTs. c-KIT was expressed markedly in canine seminomas. Both inhibin-alpha and vimentin were expressed significantly in canine SCTs. The results of this study demonstrate differences and similarities between tumor marker expression of testicular tumors in dogs and humans. All the main markers in current routine use are discussed as well as potential useful markers for benign and malignant tumors, and tumor progression.
Subject(s)
Animals , Dogs , Male , Dog Diseases/pathology , Immunohistochemistry/veterinary , Seminoma/metabolism , Sertoli Cell Tumor/metabolism , Biomarkers, Tumor/metabolismABSTRACT
Spontaneous testicular tumors, seminoma, were noticed in four male hybrid catfish (C. batrachus female x C. gariepinus male) after the age of two years. The hybrids showed massive abdominal swelling with catchectic body and free lobulated, encapsulated tumors (> 325 g) within the serosanguinous fluid-filled peritoneal cavities. The tumor cells were large and polyhedral with prominent centrally located nuclei. Other vital organs appeared normal. It seems to be the first report of seminoma in hybrid catfish and possibly of genetic cause.